Optically active grignard-type compounds and their preparation



United States Patent O "ice 3,139,442 OPTICALLY ACTIVE GRIGNARD-TYPECOM- POUNDS AND THEIR PREPARATION Bernard Rudner, Pittsburgh, andRichard A. Baiford, Delmont, Pa, assignors to Koppers Company, Inc, acorporation of Delaware No Drawing. Filed Aug. 22, 1962, Ser. No.218,566

14 Claims. (Cl. 26il345.5)

This invention relates to chemical reagents having optical activity. Inone specific aspect, it relates to new optically active Grignard-typecompounds and to a novel method of preparing such compounds.

Grignard reagents, normally prepared in an organic ether from an organichalide, RX, and magnesium, have been shown to have the structure of asolvated complex of R Mg-MgX in which there is no exchange betweenmagnesium atoms. For historical reasons the reagent is generallywritten, or referred to, as RMgX, even though this formula was found tobe incorrect by, among others, Wotiz et al., I. Am. Chem. Soc. 79, 3476(1957). Wotiz et al. proved that normal Grignard reagents, i.e. the onegenerally called ethylmagnesium bromide (existing as a solvate, possiblya polymeric form of shows practically no exchange between the two atomsof magnesium. Therefore, the generally accepted equilibrium reaction:

is, in fact, practically non-existant, while the actual equilibriuminvolved is, in its simplest form:

It is possible to prepare compounds of the formula RMgX by treating RMg-MgX with one equivalent of HX or X Such compounds function asGrignard reagents just as does R Mg-MgX Grignard alkoxides, RMgOR', inwhich the halide of the Grignard reagent is replaced by the residue ofan alcohol or phenol, have been prepared generally as unisolatedintermediates or minor components in mixtures comprising the usualGrignard halides (cf. Chemistry and Industry, 1960 1533). Similar typecompounds can be made from primary or secondary arrunes.

The Grignard reagent can exist in any one of several forms, depending onthe presence of MgX (with which R Mg forms an adduct, as is shown inEquation 2 above) or an ether or tertiary amine (with which R Mg formssolvates). Possible forms of Grignard reagents are therefore as follows:R Mg, R Mg-MgX R Mg-solvate, R Mg'MgX -solvate or polymeric formsthereof, e.g. dimers.

Quite surprisingly, we have discovered a novel class of optically activeGrignard-type alkoxides and amines of the formula RMgZR, hereinafterdefined. The R substituent of our compounds is optically active andordinarily is characterized by at least one asymmetric carbon atom. Ournew Grignard-type compounds can exist in any of the following forms:RMgZR, RMgZR'-solvate,

monomers, for example, acrylates. solvent-free form of our novelreagents is best for use 3,139,442 Patented June 30, 1964 The particularform in which the compounds of the invention are to be obtained dependsupon the their intended use, as will be explained hereafter.

The new compounds exhibit remarkable utility as vinyl polymerization andcondensation polymerization catalysts or co-catalysts and as reagents inthe chemical asymmetric synthesis of optically active alcohols.

For polymerization catalysts or co-catalysts one can use our novelcompounds in the form of optically active R Mg(ZR) its MgX adducts orits solvates, depending upon the desired reaction. Thus, halide-free,solventfree R Mg-Mg(ZR') is the most effective for condensationpolymerization and differs from conventional basic condensationcatalysts in that it is solvent soluble. The major use in polymerizationfor our novel optically active reagents is in the stereospecificpolymerization of vinyl The unsolvated or in stereospecificpolymerization.

stereospecific polymerization of an optically active monomer results inthe formation of an optically active polymer. Optical activity in apolymer results in a decrease of the entropy of the polymer; entropy inthis case being the loss of energy caused by the random arrangement ofatoms along the polymer chain. The conformation of a polymer bystereospecific synthesis results in a product having higher density andtherefore improved stiffness, improved heat distortion properties, and ahigher glass transition temperature. stereospecific polymerization of anoptically inactive monomer results in largely ordered polymerization togive an isotactic or syndiotactic polymer of improved properties.

The novel optically active reagents of the invention are also useful,particularly in the form of their halide adducts, in the asymmetricsynthesis of optically active alcohols. According to Gilman, OrganicChemistry (2nd edition), vol. 1, p. 208, asymmetric syntheses are thoseprocesses for producing optically active compounds from symmetricallyconstituted molecules by the intermediate use of optically activereagents, but without the use of any of the methods of resolution.According to Gilman, all known asymmetric syntheses by chemical meansare very inefficient, providing, at most, a 5 percent predominance ofone optically active form over its racemate. The resolution of a racemiccompound or mixture, indicated as a'l-compound, into its opticalantipodes (dcompound and I-compound) is generally a tedious andtime-consuming task involving conversion to diastereoisomericderivatives (e.g. the ddand ld-salts of dl-acid with a d-base),separation of these into pure components by fractional crystallizationand then conversion back to the desired pure isomer. Racemic tertiaryalcohols are especially diiiicult to resolve, since their ease ofdehydration makes derivatization practically impossible in someinstances. Thus, in The Resolution of Alcohols chapter 9 of vol. II ofOrganic Reactions (R. Adams, ed., John Wiley and Sons, N.Y.C., 1944) A.W. Ingersoll lists 122 alcohols successfully resolved by standardprocedures; only five of these are tertiary alcohols.

The production of optically active alcohols by reacting one of our novelGrignard-type reagents with an unsymmetrically-substituted ketone isdescribed in our co-pending application S.N. 218,567, filed even dateherewith. Because of the aforementioned difiiculty in the resolution ofa racemic mixture, an asymmetric synthesis, in which even a minorpredominance of one enantiomorph is obtained during the course of whatwould normally be the synthesis of a dl-compound, is most advantageous.

Unexpectedly, our novel asymmetric synthesis provides a 20 percentpredominance of one optically active form over its enantiomorph (e.g.l-content of product 60%,

d-content of product 40%); a degree of optical purity approximately fourtimes that normally achieved in chemical asymmetric synthesis. The novelsynthesis is quite effective for the preparation of optically activeter- In accordance With the invention We have discovered compoundsrepresentable by the formula:

RMgZR' In the above formula R is a hydrocarbon residue having i gg figsjggig of whlch 1s partlcularly dlf from 1-28 carbon atoms. R is anoptically active hydrow n to n 0 Many of the optically active alcoholsproduced by the g j gi g g i g gfi g3? g3: gg r a g f 2 foregoing methodare optically active pharmaceuticals or either oxygen wherein is eitherR or are convertible by known means to optically active phar- The tamhydrocarbon residue, defined above by thg maceutlcals; use Of the P Yacme l f as number of carbon atoms that it includes, is intended topharmaceutical intermediates IS particularly significant, mean di l d upf arbon and hydrogen only, Since y Pharmaceuticals @Xhlblt Physiologicalactlvliy free from reactive functional groups containing other typesonly in one of their optically active forms. The foreof atoms. Thus, theterm R includes alkyl, e.g. methyl, going synthesis of alcohols is veryflexible; by use of ethyl, propyl, butyl, Z-ethylhexyl, dodecyl,6-docosanyl, either the dor l-starting compound in the asymmetric andthe like; alkenyl, e.g. vinyl, isopropenyl, allyl 1- and synthesis, thefinal product will have the corresponding uta-L y and -P l y absoluteconfiguration. Pharmaceutically useful optically Y ladmdecellyl, l l/active alcohols or derivatives thereof include trihexyphenitetracosenyl,and the llke; lkmyl, ig- Z-butmyl, IO-undyl hydrochloride, useful in thetreatment of Parkinsons 20 decvynldi and the like; Cycloalkyl icydisease; alphaprodine hydrochloride, a useful analgetic; fg Fi gtridihexethyl iodide, a parasympatholytic agent particuglz f fi g y 9 ig d larly recommended for use in treating gastro-intestinal a y (Per y muormny Ti y c 1 an spasms propoxyphene hydrochloride which in its 0H1cycloaliienyl, e.g. cyclopentadieny l, phenyl, p-ethylbenzyl, Inaphthyl, l3-(cyclopent-2-enyl)tridecyl, oz-cholesteryl, 9- ioim, themost potent of tWo iacemates and four stereoflucrenyl wsiyryl bnnzhydrylcampgsteryl and the like f j 15 Sold as thefinalgesic Dan/om, butammehydro R tius includes such optically active residues as d-menthyl,ch.o11de, a commerc al local anesthetic and d -desoxyl (zcyclopamenylmethyl) l (campestel.yl, d 2 buty1 ephedrinellydl0Ci'llOllGS, used in psychogen c disorders. 4 5 d 6 any}, 1 2-henylbutyl, d-3-(l,2-allenyl)- 7 therefor? an j? 0f F Present lnventlonto benzyl, 2,6-dimethyloctyl, l-4-limoneuyl, and the like. It PTOVldfinovel Optically actlve y reagents is obvious that R must be free ofgroups that react with ful as polymerization catalysts or co-catalystsand as re- G i d e g (3501-1, and the like. agents in the synthesis ofoptically active alcohols. It is Illustrative novel compounds of theinvention (prepared a further object to provide a novel method formaking as described hereafter) in the various forms in which they theseoptically active reagents. may exist are shown below in Table I.

TABLE I N RZR -MgX 'SOIVMIG Components ame R ZR X Solvate 0HlvIethylmagnesium-d-scc- CH3- -0 CH C 21-15-11 butoxide.

Phenylmagnesium-Z-iso- 051-15 0 Br pulegoxide, magnesium bromide salt.

HgC CH3 CH3 CH3 (EH5 (EH3 (|311 (|3HCH2 CII2CII2CI{5 Allylmagnesiuml-cholestcr- CII2=CIICHz- Cli -CH oxide, tetrahydroiuranate. S l

CH; CH; z

CH3 CH3 4-Metht;x(ycyclohfiiyllmagne- CH O ZNCHC 6H5O CH; C] (0 11020 1miii ethyla hiiiiifl efm gnesium chloride salt, ethyl ctherate.

(EH3 2-0yclopentenylmethylmag- CH2 d-O CHzC C 2114 Br CEHEN nesiumd-2-methylbut0xide, l magnesium bromide salt, H pyridine solvate.

0E 2-Dimethylaminoethylmagne- NO2H4 0Q (nC.i1Iq)1O siumZ-3-sec-amy1pheuoxide, halide free, butyl etherate. OH; I

Z-H3C(|3CaE7-11 r" =9 The compounds of the invention are mostconveniently prepared by a novel method involving reacting underanhydrous, oxygen-free conditions a compound representable by theformula:

wherein X is a halogen having an atomic weight of at leats 33 and R isas defined aforesaid, with a compound representable by the formula:

wherein R and Z are as defined aforesaid.

The novel process is based on an unexpected equilibrium reaction,contrary to the findings of' Wotiz et al., illustrated by the followingequation:

The above reaction is further complicated by the presence of a Lewisbase solvent, such as an ether or tertiary amine, since the resultingGrignard-type compound is obtained in the form of its solvate.

The normal Grignard, R Mg-MgX can be prepared by any of the knownmethods described in Kharasch and Reinmuth Grignard Reactions ofNon-Metallic Substances, pp. 1'114. The simplest method is to use thedirect reaction RX+Mg, wherein R is the saturated or unsaturatedhydrocarbon residue having 1-28 carbon atoms, described hereabove. The Xof the organic halide RX must not be attached to a ternary carbon atomand can be either chlorine, bromine or iodine. It is preferable, but notnecessary, that R not be optically active. The compound R Mg-MgX may beformed in situ by adding its components RX and Mg to the reactionmixture in substantially stoichiometric quantities.

The reactant, Mg(ZR') can be made by the transesterification of Mg(ZR")with R'ZH wherein R, R" and Z have the values given hereabove. It isalso possible to prepare Mg(ZR') directly by reacting magnesium withR'ZH, although this method is not too effective in some cases. Thereaction of a metal alkyl or its hydride with R'ZH also gives thedesired compound. This method is generally the best, but it is probablymore expensive than either of the other two methods.

Mg(ZR') can also be formed in situ by the reaction of M(ZR) with aGrignard reagent as follows:

In the above equation M is a metal of Groups 1A, IIA or IHA of thePeriodic Table, Z and R are as defined above and m is the valence of themetal.

The preparation of the novel Grignard-type compounds of the invention isconducted at a temperature ranging between 50 C. and 150 C. It is morecostly, and therefore undesirable, to operate at temperatures below 50C. and at temperatures somewhat above 100 C.- 150 0., there isconsiderable danger of destroying either the reaction or the productGrignard reagent.

The reaction is conveniently conducted at atmospheric pressure, noadvantage being obtained by using lower pressures. Higher pressures maybe advantageous in the preparation of RMgX from such volatile halides asmethyl chloride or bromide.

The mole ratio of the reactants is not critical. For most purposes, itis best to use substantially stoichiometric quantities, although this isbest determined by the use to which the product will be put. Thus, forasymmetric syntheses of alcohols from our novel products plus aldehydes,etc., a slight deficiency of Mg(ZR') is generally less detrimental thana slight excess, while for use as condensation catalysts, the reverse istrue. The nature of Z also affects this: the aminides (ZNR") are morebasic then the oxides (Z=O).

peridine, dimethylaniline, and the like.

As noted hereabove, the compounds of the invention can be prepared inany one of a number of forms, depending on whether the reaction isconducted in the presence or absence of a solvent and also depending onthe work-up procedure. The reaction can be conducted in the absence of asolvent by drying milling R Mg-MgX and Mg(ZR) in an anaerobicatmosphere. If a solvent is to be used in the reaction, it must be onewhich does not destroy or is inert to the Grignard reagent. Suitablesolvents of this class include ethers, such as diethyl ether,di-n-propyl ether, di-n-butyl ether, tetrahydrofuran, Diglyme, and thelike; and tertiary amines, such as triethylamine, trimethylamine,tri-n-butylamine, tri-n-propylamine, n-methylpi- Both ethers and aminesform solvates with the product.

The product can be obtained in its halide-free form by precipitating MgXin dioxane. The unsolvated Grignard is obtained by evaporating solvatedproduct under high vacuum for a long period of time. To obtainsolvent-free RMgZR-MgX it is easiest to add Mg(ZR) to R Mg-MgX -solvatein solution and then evaporate dry under mild conditions. Solutions ofcan be made by reconstituting R Mg or by adding Mg(ZR) at any stage ofthe preparation of R Mg MgX solvate.

The novel compounds of the invention can be made by an alternate methodsomewhat similar to the Zerewitinoff procedure for the determination ofthe active hydrogen content of an alcohol. The optically active alcoholor amine, R'ZH, is reacted under anhydrous, oxygen-free conditions witha normal Grignard, according to the following equation:

This procedure is less desirable than the method according to theinvention, described hereabove, because of the destruction of one-halfof the carbon to magnesium bonds.

Suitable optically active alcohols and amines useful in the alternatemethod are menthol, neomenthol, isornenthol, carvomenthol,methylethylisopropyl carbinol, 3-methylcyclohexanol, u-methylbenzylalcohol, thujyl alcohol, borneol, desoxyephedrine, methyl-Z-butylamine,fenchyl alcohol, Z-methylmorpholine, and the like. The reaction is runusing the same pressure, temperatures, mole ratios and work-upprocedures described hereabove.

Our invention is further illustrated by the following examples:

Example 1 Magnesium l-menthoxide, Mg(OC H -l) was prepared by thereaction of clean, dry magnesium (12.1 g., 0.5 m.) with a stoichimetericquantity of distilled l-methol (156.2 g., 1 m.) in 1,2-dimethoxyethane.The same product was obtained by transesterification of magnesiumisopropoxide (14.2 g., 0.1 m.) with excess l-menthol (75 g.) at -100 C.Magnesium l-menthoxide was also made by the addition of a stoichiometricquantity of l-menthol (15.6 g., 0.1 m.) to be prepared and analyzednormal Grignard solution (ethylmagnesium bromide) in ether.

In each of the foregoing preparations, the magnesium l-menthoxideproduct was an amorphous, white solid. The three products showed thesame specific rotation, [a] -=5 1.2i0.6, at the same concentration inether. Each of the isolated products have on hydrolysis, extraction andisolation unracemized l-mentliol,

This comparsion established the equivalence of the three methods ofpreparing the solutions without racemizing the menthol.

The pure magnesium l-menthoxide, 0.00512 mole, prepared as describedhereabove, was reacted in ether with a 25 ml. of 0.41 N ethylmagnesiumbromide. The resulting product, representable as in solution, had aspecific rotation, based on the l-menthol content, of [a] =-49.6i1..Evaporation to dryness gave the theoretical weight of pyrophoricsolvate, a yellowish solid.

Example 11 Ethylmagnesium bromide was prepared in 70-89% yield by theslow addition in a dry nitrogen purged flask of 120 g. (1.1 moles) ethylbromide to a cooled, well stirred slurry of 24 g. clean, dry magnesiumin 1000 ml. dry peroxide-free ether, followed by filtration underpositive nitrogen pressure. An aliquot of the solution thus obtainedcontaining 0.40 equivalent of (C H )Mg'MgBr as its etherate wastransferred under nitrogen to another flask. The Grignard was thenslowly reacted at l5-20 C. with 31.25 g. (0.20 equivalents) purel-menthol; [a] :47.7. An exotherm developed immediately and ethane wasevolved quantitatively from the reaction mixture. There resulted aclear, colorless solution containing 0.20 equivalent of ethylmagnesiuml-menthoxide, C H MgO-C H -nMgBr -etherate. The solution thus obtainedis suitable for immediate use in the novel asymmetric synthesis ofalcohols, illlustrated by Example XIII. For characterization, andespecially for polymerization, it is desirable to prepare salt-free orsolventfree ethylmagnesium l-menthoxide.

Example III The solution of Example II, containing the novel Grignardwas distilled under nitrogen at low temperatures to remove most of thediethyl ether then under nitrogen pressure pumped for 24 hours at 0.5mm. to remove all solvent and solvate liquid. There resulted aquantitative yield of ether-free ethylmagnesium l-menthoxide-MgBr a paleyellow, microcrystalline sold, which was highly pyrophoric. In a sealedtube under nitrogen the crystals decomposed with gas evolution, ratherthan melting. The crystals were soluble, except for a trace, in dryheptane.

Example IV To prepare salt-free ethylmagnesium l-menthoxide for use as acondensation catalyst, it is best to remove salt from (C H Mg-MgBr-etherate. Normal Grignard bromide was prepared from 24 g. drymagnesium, 130 g. ethyl bromide and 1000 g. of ether. The mixture wastreated with 115 g. (1.3 moles) of dry, peroxide-free dioxane in anequal volume of dry, peroxide-free ether. The resulting mixture wasstirred for eight hours under nitrogen, then filtered free ofprecipitated salt. The addition to the filtrate of one mole of l-mentholper mole of diethyl magnesium at l015 C. gave a clear solution of thenovel optically active Grignard, representable by either of theequilibrium (solvated) forms:

The product was obtained in an amount corresponding to 63 percent of thetheoretical yield. None of the bromide remained in solution. In thisform, as its bromide-free solvate in dioxane, ethylmagnesiuml-menthoxide is more effective as a condensation catalyst andco-catalyst in a free radical polymerization system (cf. Example XV),than in asymmetric synthesis or ionic polymerization catalyst systems.

The clear solution was distilled at slightly above room temperature toremove ether, then held at 70-80 C. at 1 mm. for 48 hours to removedioxane. The solid product, representing 48 percent yield of activeGrignard, was obtained as a dry, amorphous, pyrophoric, off-white solid,free of ether and dioxane and essentially free of bromide ion. In thisform the product is a good condensation catalyst, but it is now mostefiective in ionic polymerization catalyst systems, giving good yieldsof optically active polymer. Visually, this product is practicallyidentical with the dried Grignard alkoxides of Examples I and III.

The same product can be obtained by slurrying the solid ether-freemagnesium bromide adduct of ethylmagnesium l-menthoxide with equimolaramounts of dry dioxane for four hours, followed by filtering andevaporating the filtrate down to dryness in vacuo.

Example V The procedure of Example II was repeated with the exceptionthat all-menthol was substituted for the l-menthol used as a reactant. Avisually identical product was obtained, but the product had no opticalactivity.

Example VI A solution was made by slowly adding 12.9 g. pure d-2-octanol in 100 ml. diethyl ether at 1520 C. with agitation to 100 ml. of2.15 N ethylmagnesium bromide in ether. The resulting product gave thesame specific rotation, based on Z-octanol, as did a solution preparedfrom magnesium d-2-octoxide and ethylmagnesium bromide. Both productGrignard-type compounds showed the same visual properties and achievedthe same asymmetric induction with acetophenone.

Example VII The procedure of Example VI was repeated usingphenylmagnesium bromide in lieu of the ethylmagnesium bromide as theGrignard reagent. There was thus obtained as an unisolated productphenylmagnesium d-2- octoxide.

Example VIII A solution of 30.25 g. d-desoxyephedrine and 30 ml. ofdi-n-butyl ether was slowly added to 400 ml. of di-nbutyl ethercontaining 0.406 mole of ethylmagnesium bromide. The resulting mixturewas heated at C. for

30 minutes. The product thus obtained was identical in its properties toone made by heating unisolated.

H CH3 ooH OHzd1 IM Br made from heating a 1:2 molar mixture ofethylmagnesium bromide and desoxyephedrine in refluxing dibutyl etherfor thirty minutes.

Example IX The procedure of Example VIII was repeated usingmethylmagnesium bromide as the Grignard reagent. There was thus obtaineda Grignard-type compound having the formula:

r CHghIgN-C H CHZC 5H5 Example X Methylmagnesium cholesteroxide was madein low yield from 200 ml. 1.5 N methylmagnesium iodide in ether and 58g. of cholesterol in 600 ml. ether. The product appeared as a viscousinhomogeneous semi-solid.

Example XI A solution of phenylmagnesium chloride was made in 43 percentyield by refluxing a stirred suspension of 5 g. magnesium metal and acatalytic amount of ethyl iodide in 500 ml. of purified chlorobenzenefor 48 hours under dry nitrogen. An aliquot of the filtrate containing0.4 g. of (C H Mg-MgCl was transferred anaerobically to a smaller flaskand stirred at 20-25 C. under dry nitrogen while being treated over aperiod of 25 minutes with a solution of 0.625 (slightly less than onemole of alcohol per mole of Grignard) a-d-tocopherol in 15 ml. ofchlorobenzene. The reaction mixture was stirred at 60-70 C. for one-halfhour and then taken to dryness in vacuo.

The weight of the residue was approximately that theoretically requiredfor the monosolvate:

The thick, brown, oily phenylmagnesium-d-ot-tocopheroxide in benzene hadan optical rotation of --0.86.

Example XII To stirred dried magnesium, 12 g., there was slowly addedunder nitrogen at room temperature 66.3 g. pure benzyl chloride in 70ml. diethyl ether. The Grignard reagent precipitated as formed as awhite, amorphous solid. An additional 200 ml. of diethyl ether was addedand the stirring was continued while a solution of 37.4 g. l-borneol in100 m1. of ether was added over a three hour period. The exothermresulting from the addition of the l-borneol required the use of a waterbath. An aliquot of this suspension, corresponding to calculated 1.5 g.benzylmagnesium-l-borneoxide was transferred anaerobically to anotherflask. It was evaporated dry at about mm. of Hg and 2030 C. to give aWhite, amorphous pyrophoric polyetherate. The product was soluble inperoxide-free dioxane. After being filtered free of precipitatedmagnesium chloride, the halide-free off-white solution had an opticalrotation of 13.8. On calculated borneol content this rotation is aboutthe same as a dioxane solution obtained on dissolving the evaporatedresidue of a benzylmagnesium-l-borneoxide Was transferred anaerobicallyto ether.

Example XIII 1 [0.185 mole, 1 equivalent per equivalent of pure l-metholin 200 ml. of ether. The reaction mixture was stirred for 30 minutes.After the addition of l-methol, there was thereafter added 20 g.distilled methylisobutyl ketone in 150 ml. of ether. The mixture wasallowed to react and then hydrolyzed with a saturated aqueous ammoniumchloride solution. The dry ether layer was stripped off and the productwas distilled to give 67 percent of the theoretical yield of puremethylisobutylcarbinol (3,5-dimethyl-3-hexanol, B.P. 55.8-56.1 at 15mm.). The product was purified by vapor-phase chromatography andrefractionation at both reduced pressure (B.P. 56.3-56.6 at 15 mm.) andagain at atmospheric pressure (B.P. 152 0., literature reports 152-153C.). The specific rotation of the pure product [oc] =0.45, correspondingto 83 percent dl-carbinol and 17 percent l-carbinol. Distillation of theresidues gave additional amounts of product having about the samespecific rotation. Infrared spectra and vapor phase chromatography ofproduct cuts showed complete absence of ketones, olefins or l-menthol.

Example XIV Sodium-l-menthoxide was prepared in heptane from 4.2 g.sodium and 25 g. l-menthol. When the reaction ceased, the mixture wasfiltered free of excess sodium to give, by titration, a 0.6 N solutionrepresenting a quantitative yield of sodium-l-menthoxide, [0t]:14.5i0.3, specific rotation. During this time, cyclohexylmagnesiumbromide was made from /2 mole magnesium and /2 mole distilledcyclohexylbromide in diethyl ether. After clarifying, the solution wasevaporated down and thereafter held for three days at 0.5-3 mm. of Hgand 3032 C. until no more loss of weight was observed. Titration showeda 62 percent yield of (C H )Mg-MgBr The Grignard was taken up in tolueneto give an 0.2 molar solution. The two solutions were mixed instoichometric quantities (2 moles of alkoxide to one mole of Grignard)and stirred for two hours at room temperature. The

reaction mixture was clarified free of sodium to give a clear, lightbrown solution of representing an 84 percent yield based on the amountof sodium bromide precipitated.

Example XV At 25-30 C. the toluene solution of the product of ExampleXIV, containing 0.1 g. of Grignard menthoxide, was diluted with tolueneto 200 ml. It was then treated dropwise with 0.2 g. titaniumtetrachloride in ml. of toluene, and stirred one-half hour at roomtemperature. There was then added dropwise over a 30 minute period 50ml. distilled methylmethacrylate. The resulting polymerization mixturewas stirred at 2530 C. for eight hours and filtered under anaerobicconditions. The polymeric product was washed well with toluene to give acrystalline polymet-hylmethacrylate, very slightly levorotary.

We claim:

1. A compound representable by the formula:

wherein R is a hydrocarbon residue selected from the group consisting ofalkyl, alkenyl, alkinyl, cycloalkyl and cycloalkenyl having from 1-28carbon atoms; R is an optically active hydrocarbon residue selected fromthe group consisting of alkyl, alkenyl, alkinyl, cycloalkyl andcycloalkenyl having from 4-28 carbon atoms, at least one of said carbonatoms being asymmetric; and Z is a member selected from the groupconsisting of O- and N-R", wherein R is a member selected from the groupconsisting of R and R.

2. A halide-associated compound representable by the formula:

wherein R is a hydrocarbon residue selected from the group consisting ofalkyl, alkenyl, alkinyl, cycloalkyl and cycloalkenyl having from 1-28carbon atoms; R is an optically active hydrocarbon residue selected fromthe group consisting of alkyl, alkenyl, alkinyl, cycloalkyl andcycloalkenyl having from 4-28 carbon atoms, at least one of said carbonatoms being asymmetric; and Z is a member selected from the groupconsisting of -O-- and NR", wherein R" is a member selected from thegroup consisting of R and R.

3. A halide-associated, solvated compound representable by the formula:

wherein R is a hydrocarbon residue selected from the group consisting ofalkyl, alkenyl, alkinyl, cycloalkyl and cycloalkenyl having from 1-28carbon atoms; R' is an optically active hydrocarbon residue selectedfrom the group consisting of alkyl, alkenyl, alkinyl, cycloalkyl andcycloalkenyl having from 4-28 carbon atoms, at least one of said carbonatoms being asymmetric; and Z is a member selected from the groupconsisting of -0 and N-R", wherein R" is a member selected from thegroup consisting of R and R.

4. Ethylmagnesium-l-menthoxide.

5. Magnesium bromide-associated ethylmagnesium-vmenthoxide.

6. Magnesium bromide-associated, diethyl ether-solvatedethylmagnesium-bmenthoxide.

7. Magnesium bromide-associated diethyl ether-solvatedphenylmagnesium-l-Z-octoxide.

8. Magnesium bromide-associated diethyl ethler-solvated methylmagnesiumcholesteroxide.

9. Magnesium bromide-associated diethyl ether-solvated methylmagnesiumdesoxyephedride.

10. Magnesium bromideassociated diethyl ether-solvatedphenylmagnesium-l-borneoxide.

11. Magnesium chloride-associated, chlorobenzene-solvatedphenylmagnesiurn a-dstocopheroxide.

11 12. Method of making a compound representable by the formula:

RMgZR' wherein R is a hydrocarbon residue selected from the groupconsisting of alkyl, alkenyl, alkinyl, cycloalkyl and cycloalkenylhaving from 1-28 carbon atoms; R is an optically active hydrocarbonresidue selected from the group consisting of alkyl, alkenyl, alkinyl,cycloalkyl and cycloalkenyl having from 4-28 carbon atoms, at least oneof said carbon atoms being asymmetric; and Z is a member selected fromthe group consisting of O and NR", wherein R is a member selected fromthe group consisting of R and R, comprising reacting under anhydrousoxygen-free conditions a compound representable by the formula:

R Mg'Mgx wherein X is a halogen having an atomic weight of at 12 least33 and R is as defined aforesaid, with a compound representable by theformula:

References Cited in the file of this patent UNITED STATES PATENTS MarkerSept. 9, 1941 Marker Sept. 9, 1941 UNITED STATES PATENT OFFICECERTIFICATE OF CORRECTION Patent No 3 ,139 ,442 June 30 1964 BernardRudner et al.

n the above numbered pattified that error appears i nt should read as Itis hereby cer ent requiring correction and that the said Letters Patecorrected below.

line 10, for "R Mg(ZR read R m n unq for "methol" read solid columnthylmagne'sium-lmenthol 10, line Column 2, Column 6, line 55, column 7,line 38, for "sold" read 62, for "ethylmagnesiumv read e Signed andsealed this 20th day. of July 1965.

(SEAL) Attest: ERNEST W. SWIDER EDWARD J BRENNER Commissioner of PatentsAitesting Officer

1. A COMPOUND REPRESENTABLE BY THE FORMULA:
 11. MAGNESIUM CHLORIDE-ASSOCIATED, CHLOROBENZENE-SOLVATED PHENYLMAGNESIUM-A-D-TOCOPHEROXIDE.